Nitrogen electro-reduction under mild conditions is one promising alternative approach of the energyconsuming Haber-Bosch process for the artificial ammonia synthesis.One critical aspect to unlocking this technology i...Nitrogen electro-reduction under mild conditions is one promising alternative approach of the energyconsuming Haber-Bosch process for the artificial ammonia synthesis.One critical aspect to unlocking this technology is to discover the catalysts with high selectivity and efficiency.In this work,the N_(2)-to-NH_(3)conversion on the functional MoS_(2)is fully investigated by density functional theory calculations since the layered MoS_(2)provides the ideal platform for the elaborating copies of the nitrogenase found in nature,wherein the functionalization is achieved via basal-adsorption,basal-substitution or edge-substitution of transition metal elements.Our results reveal that the edge-functionalization is a feasible strategy for the activity promotion;however,the basal-adsorption and basal-substitution separately suffer from the electrochemical instability and the NRR inefficiency.Specifically,MoS_(2)functionalized via edge W-substitution exhibits an exceptional activity.The energetically favored reaction pathway is through the distal pathway and a limiting potential is less than 0.20 V.Overall,this work escalates the rational design of the high-effective catalysts for nitrogen fixation and provides the explanation why the predicated catalyst have a good performance,paving the guidance for the experiments.展开更多
Growing evidence suggests that breast cancer cell plasticity arises due to a partial reactivation of epithelialmesenchymal transition(EMT) programs in order to give cells pluripotency, leading to a stemness-like pheno...Growing evidence suggests that breast cancer cell plasticity arises due to a partial reactivation of epithelialmesenchymal transition(EMT) programs in order to give cells pluripotency, leading to a stemness-like phenotype. A complete EMT would be a dead end program that would render cells unable to fully metastasize to distant organs. Evoking the EMT-mesenchymal-toepithelial transition(MET) cascade promotes successful colonization of distal target tissues. It is unlikely that direct reprogramming or trans-differentiation without passing through a pluripotent stage would be thepreferred mechanism during tumor progression. This review focuses on key EMT transcriptional regulators, EMT-transcription factors involved in EMT(TFs) and the mi RNA pathway, which are deregulated in breast cancer, and discusses their implications in cancer cell plasticity. Cross-regulation between EMT-TFs and mi RNAs, where mi RNAs act as co-repressors or co-activators, appears to be a pivotal mechanism for breast cancer cells to acquire a stem cell-like state, which is implicated both in breast metastases and tumor recurrence. As a master regulator of mi RNA biogenesis, the ribonuclease type Ⅲ endonuclease Dicer plays a central role in EMTTFs/mi RNAs regulating networks. All these EMT-MET key regulators represent valuable new prognostic and predictive markers for breast cancer as well as promising new targets for drug-resistant breast cancers.展开更多
In healthy people,balance between glucose production and its utilization is precisely controlled.When circulating glucose reaches a critical threshold level,pancreaticβcells secrete insulin that has two major actions...In healthy people,balance between glucose production and its utilization is precisely controlled.When circulating glucose reaches a critical threshold level,pancreaticβcells secrete insulin that has two major actions:to lower circulating glucose levels by facilitating its uptake mainly into skeletal muscle while inhibiting its production by the liver.Interestingly,dietary triglycerides are the main source of fatty acids to fulfill energy needs of oxidative tissues.Normally,the unconsumed fraction of excess of fatty acids is stored in lipid droplets that are localized in adipocytes to provide energy during fasting periods.Thus,adipose tissue acts as a trap for fatty acid excess liberated from plasma triglycerides.When the buffering action of adipose tissue to store fatty acids is impaired,fatty acids that build up in othertissues are metabolized as sphingolipid derivatives such as ceramides.Several studies suggest that ceramides are among the most active lipid second messengers to inhibit the insulin signaling pathway and this review describes the major role played by ceramide accumulation in the development of insulin resistance of peripherals tissues through the targeting of specific proteins of the insulin signaling pathway.展开更多
AIM:To assess the symptomatic efficacy of Lactobacillus plantarum 299v(L.plantarum 299v)(DSM 9843) for the relief of abdominal symptoms in a large subset of irritable bowel syndrome(IBS) patients fulfilling the Rome ...AIM:To assess the symptomatic efficacy of Lactobacillus plantarum 299v(L.plantarum 299v)(DSM 9843) for the relief of abdominal symptoms in a large subset of irritable bowel syndrome(IBS) patients fulfilling the Rome Ⅲ criteria.METHODS:In this double blind,placebo-controlled,parallel-designed study,subjects were randomized to daily receive either one capsule of L.plantarum 299v(DSM 9843) or placebo for 4 wk.Frequency and intensity of abdominal pain,bloating and feeling of incomplete rectal emptying were assessed weekly on a visual analogue scale while stool frequency was calculated.RESULTS:Two hundred and fourteen IBS patients were recruited.After 4 wk,both pain severity(0.68 + 0.53 vs 0.92 + 0.57,P < 0.05) and daily frequency(1.01 + 0.77 vs 1.71 + 0.93,P < 0.05) were lower with L.plantarum 299v(DSM 9843) than with placebo.Similar results were obtained for bloating.At week 4,78.1 % of the patients scored the L.plantarum 299v(DSM 9843) symptomatic effect as excellent or good vs only 8.1 % for placebo(P < 0.01).CONCLUSION:A 4-wk treatment with L.plantarum 299v(DSM 9843) provided effective symptom relief,particularly of abdominal pain and bloating,in IBS patients fulfilling the Rome Ⅲ criteria.展开更多
The recent discovery of cancer cell plasticity,i.e.their ability to reprogram into cancer stem cells(CSCs)either naturally or under chemotherapy and/or radiotherapy,has changed,once again,the way we consider cancer tr...The recent discovery of cancer cell plasticity,i.e.their ability to reprogram into cancer stem cells(CSCs)either naturally or under chemotherapy and/or radiotherapy,has changed,once again,the way we consider cancer treatment.If cancer stemness is a reversible epigenetic state rather than a genetic identity,opportunities will arise for therapeutic strategies that remodel epigenetic landscapes of CSCs.However,the systematic use of DNA methyltransferase and histone deacetylase inhibitors,alone or in combination,in advanced solid tumors including colorectal cancers,regardless of their molecular subtypes,does not seem to be the best strategy.In this review,we first summarize the knowledge researchers have gathered on the epigenetic signatures of CSCs with the difficulty of isolating rare populations of cells.We raise questions about the relevant use of currently available epigenetic inhibitors(epidrugs)while the expression of numerous cancer stem cell markers are often repressed by epigenetic mechanisms.These markers include the three cluster of differentiation CD133,CD44 and CD166 that have been extensively used for the isolation of colon CSCs.and.Finally,we describe current treatment strategies using epidrugs,and we hypothesize that,using correlation tools comparing associations of relevant CSC markers with chromatin modifier expression,we could identify better candidates for epienzyme targeting.展开更多
Hepatitis C virus(HCV) infects hepatocytes, polarized cells in the liver. Chronic HCV infection often leads to steatosis, fibrosis, cirrhosis and hepatocellular carcinoma, and it has been identified as the leading cau...Hepatitis C virus(HCV) infects hepatocytes, polarized cells in the liver. Chronic HCV infection often leads to steatosis, fibrosis, cirrhosis and hepatocellular carcinoma, and it has been identified as the leading cause of liver transplantation worldwide. The HCV replication cycle is dependent on lipid metabolism and particularly an accumulation of lipid droplets in host cells. Phosphoinositides(PIs) are minor phospholipids enriched in different membranes and their levels are tightly regulated by specific PI kinases and phosphatases. PIs are implicated in a vast array of cellular responses that are central to morphogenesis, such as cytoskeletal changes, cytokinesis and the recruitment of downstream effectors to govern mechanisms involved in polarization and lumen formation. Important reviews of the literature identified phosphatidylinositol(Ptd Ins) 4-kinases, and their lipid products Ptd Ins(4)P, as critical regulators of the HCV life cycle. SH2-containing inositol polyphosphate 5-phosphatase(SHIP2), phosphoinositide 3-kinase(PI3K) and their lipid products Ptd Ins(3,4)P2 and Ptd Ins(3,4,5)P3, respectively, play an important role in the cell membrane and are key to the establishment of apicobasal polarity and lumen formation. In this review, we will focus on these new functions of PI3 K and SHIP2, and their deregulation by HCV, causing a disruption of apicobasal polarity, actin organization and extracellular matrix assembly. Finally we will highlight the involvement of this pathway in the event of insulin resistance and nonalcoholic fatty liver disease related to HCV infection.展开更多
Few studies have analyzed the effect of ve- nous thromboembolism (VTE) events on the prognosis of pancreatic cancer, but their results were conflicting. The pres- ent study was undertaken to determine the effect of ...Few studies have analyzed the effect of ve- nous thromboembolism (VTE) events on the prognosis of pancreatic cancer, but their results were conflicting. The pres- ent study was undertaken to determine the effect of VTE on pancreatic adenocarcinoma (PA) outcomes. METHODS: All consecutive patients diagnosed with PA from May 2004 to January 2012 in a single oncology center were retrospectively studied. Clinical, radiological and histologi- cal data at time of diagnosis or within the first 3 months after surgery, including the presence (+) or absence (-) of VTE were collected. VTE was defined as radiological evidence of either pulmonary embolism (PE), deep venous thrombosis without infection or catheter-related thrombosis. PA with and without PE was compared for survival using the Kaplan-Meier method to estimate overall survival. RESULTS: Among 162 PA patients with a median follow-up of 15 (3-92) months after diagnosis, 28 demonstratedVTE (+). PA patients with and without PE were similar for age, American Society of Anesthesiologist score, body mass index, and histo- ry of treatment. The distribution of cancer stages was similarbetween the two groups VTE (+) and VTE (-). The median du- ration of survival was significantly worse in the VTE (+) group vs VTE (-) (12 vs 18 months, P=0.010). In multivariate analysis, the presence of VTE and surgical treatment were independent prognostic factors for overall survival. CONCLUSION: VTE (+) at time of diagnosis or within the first 3 months after surgery during treatment is an indepen- dent factor of poor prognosis in PA.展开更多
Launaea taraxacifolia is a leafy vegetable of the family of Asteraceae (Compositae) found in several countries in West Africa including Ghana, Benin and Nigeria. The plant leaves are eaten either fresh as salad or coo...Launaea taraxacifolia is a leafy vegetable of the family of Asteraceae (Compositae) found in several countries in West Africa including Ghana, Benin and Nigeria. The plant leaves are eaten either fresh as salad or cooked as sauces. They are also consumed as infusion to fight against several diseases including non-communicable diseases such as diabetes and hypertension. Several studies have been conducted in Ghana, Nigeria on the nutritional and medicinal values of this plant but no study has yet been conducted in Benin on the virtues of this plant. In this work we have achieved the phytochemical characterization and evaluated the cytotoxicity as well as hypolipidemic and anti-oxidant effects of the ethanol-aqueous extracts of Launaea taraxacifolia leaves. Cytotoxicity and hypolipidemic activities have been performed on HepG2 cells;the antioxidant effect has been performed on the PLB985 cells. The results showed that the ethanol-aqueous extracts of Launaea taraxacifolia leaves contained the following metabolites: catechic tannin, flavonoids, phenolic acids, mucilage and leucoanthocyanins. Only very high concentrations (>20 mg/ml) of leaves extracts are toxic for HepG2 cells. Launaea taraxacifolia leaves have significant antioxidant and hypolipidemic activities.展开更多
In the world,among all type of cancers,colorectal cancer(CRC)is the third most commonly diagnosed in males and the second in females.In most of cases,(RP1)patients’prognosis limitation with malignant tumors can be at...In the world,among all type of cancers,colorectal cancer(CRC)is the third most commonly diagnosed in males and the second in females.In most of cases,(RP1)patients’prognosis limitation with malignant tumors can be attributed to delayed diagnosis of the disease.Identification of patients with early-stage disease leads to more effective therapeutic interventions.Therefore,new screening methods and further innovative treatment approaches are mandatory as they may lead to an increase in progression-free and overall survival rates.For the last decade,the interest in extracellular vesicles(EVs)research has exponentially increased as EVs generation appears to be a universal feature of every cell that is strongly involved in many mechanisms of cell-cell communication either in physiological or pathological situations.EVs can cargo biomolecules,such as lipids,proteins,nucleic acids and generate transmission signal through the intercellular transfer of their content.By this mechanism,tumor cells can recruit and modify the adjacent and systemic microenvironment to support further invasion and dissemination.This review intends to cover the most recent literature on the role of EVs production in colorectal normal and cancer tissues.Specific attention is paid to the use of EVs for early CRC diagnosis,follow-up,and prognosis as EVs have come into the spotlight of research as a high potential source of‘liquid biopsies’.The use of EVs as new targets or nanovectors as drug delivery systems for CRC therapy is also summarized.展开更多
There is an increasing interest in developing nanoparticles with diverse biologic activities.To this end,we prepared 10 to 15 nm silver nanoparticles(AgNP)from native isolates of Trichoderma atroviride.Within this stu...There is an increasing interest in developing nanoparticles with diverse biologic activities.To this end,we prepared 10 to 15 nm silver nanoparticles(AgNP)from native isolates of Trichoderma atroviride.Within this study,endophytic fungi hosted four medicinal plants in Saint Katherine Protectorate,South Sinai,Egypt have been isolated by surface sterilization technique on four isolation media.Ten species,based on their frequency of occurrence,out of twenty recovered taxa were tested for their capability to synthesize extracellular AgNPs.Trichoderma atroviride hosted Chiliadenus montanus was found to be the best candidate for the production of mycogenic AgNPs among all examined species.The mycosynthesized AgNPs were compared with chemically synthesized and characterized using Ultraviolet-visible(UV-vis)spectroscopy,Raman spectroscopy,X-ray diffraction(XRD)and high-resolution transmission electron microscopy(HRTEM)techniques.The HRTEM result showed the distribution of spherical AgNPs ranging from 10 to 15 nm.Trichoderma atroviride isolate was subjected to sequencing for confirmation of phenotypic identification.The internal transcribed spacer(ITS)1-5.8 s-ITS2 rDNA sequences obtained were compared with those deposited in the GenBank Database and registered with accession number MH283876 in the NCBI Database.Antibacterial,anticandidal and antifungal effects of chemically and mycosynthesized AgNPs were examined at various concentrations in vitro against six pathogenic bacteria and 4 pathogenic fungi by agar well diffusion technique.Standard antibiotics;Gentamicin,Amoxicillin,Clotrimazole,and Nystatin at 5μg/disk were taken as positive controls,while 5%DMSO was used as the negative control.Our data revealed that the application of mycogenic AgNPs at a concentration of 100 ppm resulted in maximum inhibition of pathogenic bacteria and fungi.These data suggest that AgNPs from native isolates of Trichoderma atroviride(MH283876)offer a source of rapid synthesis of eco-friendly,economical biomaterials that show antimicrobial activities.展开更多
Hepatocellular carcinoma(HCC)is one of the leading causes of cancer related death in Asia and Africa(1).It reflects the high burden of hepatitis B virus(HBV)infection in these areas.Curative treatments of HCC as...Hepatocellular carcinoma(HCC)is one of the leading causes of cancer related death in Asia and Africa(1).It reflects the high burden of hepatitis B virus(HBV)infection in these areas.Curative treatments of HCC as radiofrequency ablation and resection are impaired by a high rate of tumor recurrence.However,most of the time,HCC is frequently diagnosed at advanced stages where only展开更多
The Beni Bousera massif(Rifean belt,northern Morocco)is predominantly composed of spinel lherzolite with subordinate garnet pyroxenite and garnet peridotite layers.It formed an antiformal dome which was overlain by gr...The Beni Bousera massif(Rifean belt,northern Morocco)is predominantly composed of spinel lherzolite with subordinate garnet pyroxenite and garnet peridotite layers.It formed an antiformal dome which was overlain by graphite-sillimanite-garnet gneisses(kinzigites)equilibrated at around 1 GPa and 750℃.Within these kinzigites,kyanite-bearing basic granulites record somewhat higher PT conditions of around 1.6-2.0 GPa and 760-820℃.Garnet clinopyroxenite(either graphite-bearing or graphi-展开更多
AIM:To assess,in a routine practice setting,the sus-tained virologic response(SVR) to telaprevir(TPV) or boceprevir(BOC) in hepatitis C virus(HCV) nullresponders or relapsers with severe liver fibrosis.METHODS:One hun...AIM:To assess,in a routine practice setting,the sus-tained virologic response(SVR) to telaprevir(TPV) or boceprevir(BOC) in hepatitis C virus(HCV) nullresponders or relapsers with severe liver fibrosis.METHODS:One hundred twenty-five patients were treated prospectively for 48 wk with TPV or BOC + pegylated-interferon(peg-INF) α2a + ribavirin(PR) according to standard treatment schedules without randomization.These patients were treated in routine practice settings in 10 public or private health care centers,and the data were prospectively collected.Only patients with severe liver fibrosis(Metavir scores of F3 or F4 upon liver biopsy or liver stiffness assessed by elastography),genotype 1 HCV and who were null-responders or relapsers to prior PR combination therapy were included in this study.RESULTS:The Metavir fibrosis scores were F3 in 35(28%) and F4 in 90(72%) of the patients.In total,62.9% of the patients were null-responders and 37.1% relapsers to the previous PR therapy.The overall SVR rate at 24 wk post-treatment withdrawal was 59.8%.The SVR was 65.9% in the TPV group and 44.1% in the BOC group.Independent predictive factors of an SVR included a response to previous treatment,relapsers vs null-responders [OR = 3.9;(1.4,10.6),P = 0.0084],a rapid virological response(RVR) [OR 6.9(2.6,18.2),P = 0.001] and liver stiffness lower than 21.3 kPa [OR = 8.2(2.3,29.5),P = 0.001].During treatment,63 patients(50.8%) had at least one severe adverse event(SAE) of grade 3 or 4.A multivariate analysis identified two factors associated with SAEs:female gender [OR = 2.4(1.1,5.6),P = 0.037] and a platelet count below 150 × 103/ mm3 [OR = 5.3(2.3,12.4),P ≤ 0.001].CONCLUSION:More than half of these difficult-to-treat patients achieved an SVR and had SAEs in an actual practice setting.The SVR rate was influenced by the response to previous PR treatment,the RVR and liver stiffness.展开更多
In this work, we study the smoothing effect of Cauchy problem in Sobolev space for the spatially homogeneous Landau equation in the Maxwellian case. We obtain a precise estimate with respect to time variable, which im...In this work, we study the smoothing effect of Cauchy problem in Sobolev space for the spatially homogeneous Landau equation in the Maxwellian case. We obtain a precise estimate with respect to time variable, which implies the ultra-analytic effect of weak solutions.展开更多
The presence of solid particles or water droplets in continuous fluid flow can either induce turbulence attenuation or amplification. The modification of the state of the turbulence depends on the characteristics of t...The presence of solid particles or water droplets in continuous fluid flow can either induce turbulence attenuation or amplification. The modification of the state of the turbulence depends on the characteristics of the particles, such as volume fraction, mean diameter, mass density, or carrier phase flow properties. In this brief review, the main physical concepts related to the most important physical aspects of turbulence modulation are summarized. Different criteria used to distinguish the enhancement or the attenuation effects of the particles on the carrier phase flows are recalled. For the interest of large-scale industrial applications, several theoretical,experimental and empirical approaches are discussed, which provides an interesting framework for the study of the effect of particles on turbulence behavior modification.展开更多
This review is concerned with the effect of the addition of zirconium as a third element on the heat-resisting properties of Fe_3Al intermetallic compounds and explains their high-temperature oxidation mechanism.The F...This review is concerned with the effect of the addition of zirconium as a third element on the heat-resisting properties of Fe_3Al intermetallic compounds and explains their high-temperature oxidation mechanism.The Fe_3Al and Fe_3Al-0.05Zr specimens were isothermally oxidized in the temperature range of 1173~1473 K in synthetic air for 100 h.The formation of the alumina layer approximately obeyed the parabolic rate law,with the exception of short initial stage.The parabolic rate constant values for the Zr-doped Fe_3Al decreased at all tested temperatures.Fe_3Al revealed massive spallation,whereas Fe_3AlZr produced a flat,adherent oxide layer.The microstructure investigations of the alumina scales grown thermally on the Fe_3Al-Zr alloy by means of SEM-EDS showed that they were 1.5~2μm thick and consisted of a small inner columnar layer and an equiaxed outer grain layer.Additionally,very fine(50~150 nm) oxide particles rich in Zr were found across the alumina scales.The addition of Zr significantly affected the oxidation behavior of Fe_3Al by improving the adherence of theα-Al_2O_3 scale.TEM-SAD investigations of the alumina scales on samples prepared using the FIB(Focused Ion Beam) method confirmed the presence of small tetragonal zirconia grains near the scale/gas and alloy/scale interfaces,most of which were formed along alumina grain boundaries(gbs).Zr gb-segregation was found using HRTEM.The role of preferential formation of zirconium oxide along the alumina scale grain boundaries and the effect of Zr gb-segregation on oxidation and scale growth mechanisms were analyzed by means of two-stage oxidation experiments using ^(16)O_2/^(18)O_2.The SIMS oxygen isotope profiles for the Fe_3Al-Zr alloy oxidized at 1373 K, after two-stage oxidation experiments,revealed that oxygen anion diffusion is predominant compared to that of aluminum cation diffusion.展开更多
BACKGROUND When combined with vanadium salts,catecholamines strongly activate glucose uptake in rat and mouse adipocytes.AIM To test whether catecholamines activate glucose transport in human adipocytes.METHODS The up...BACKGROUND When combined with vanadium salts,catecholamines strongly activate glucose uptake in rat and mouse adipocytes.AIM To test whether catecholamines activate glucose transport in human adipocytes.METHODS The uptake of 2-deoxyglucose(2-DG)was measured in adipocytes isolated from pieces of abdominal subcutaneous tissue removed from women undergoing reconstructive surgery.Pharmacological approaches with amine oxidase inhibitors,adrenoreceptor agonists and antioxidants were performed to unravel the mechanisms of action of noradrenaline or adrenaline(also named epinephrine).RESULTS In human adipocytes,45-min incubation with 100μmol/L adrenaline or noradrenaline activated 2-DG uptake up to more than one-third of the maximal response to insulin.This stimulation was not reproduced with millimolar doses of dopamine or serotonin and was not enhanced by addition of vanadate to the incubation medium.Among various natural amines and adrenergic agonists tested,no other molecule was more efficient than adrenaline and noradrenaline in stimulating 2-DG uptake.The effect of the catecholamines was not impaired by pargyline and semicarbazide,contrarily to that of benzylamine or methylamine,which are recognized substrates of semicarbazide-sensitive amine oxidase.Hydrogen peroxide at 1 mmol/L activated hexose uptake but not pyrocatechol or benzoquinone,and only the former was potentiated by vanadate.Catalase and the phosphoinositide 3-kinase inhibitor wortmannin inhibited adrenaline-induced activation of 2-DG uptake.CONCLUSION High doses of catecholamines exert insulin-like actions on glucose transport in human adipocytes.At submillimolar doses,vanadium did not enhance this catecholamine activation of glucose transport.Consequently,this dismantles our previous suggestion to combine the metal ion with catecholamines to improve the benefit/risk ratio of vanadium-based antidiabetic approaches.展开更多
Along with the development of big data, various Natural Language Generation systems (NLGs) have recently been developed by different companies. The aim of this paper is to propose a better understanding of how these s...Along with the development of big data, various Natural Language Generation systems (NLGs) have recently been developed by different companies. The aim of this paper is to propose a better understanding of how these systems are designed and used. We propose to study in details one of them which is the NLGs developed by the company Nomao. First, we show the development of this NLGs underlies strong economic stakes since the business model of Nomao partly depends on it. Then, thanks to an eye movement analysis conducted with 28 participants, we show that the texts generated by Nomao’s NLGs contain syntactic and semantic structures that are easy to read but lack socio-semantic coherence which would improve their understanding. From a scientific perspective, our research results highlight the importance of socio-semantic coherence in text-based communication produced by NLGs.展开更多
基金financial support from the National Natural Science Foundation of China(21503097,52130101,51701152,21806023,and 51702345)China Scholarship Council(202008320215).
文摘Nitrogen electro-reduction under mild conditions is one promising alternative approach of the energyconsuming Haber-Bosch process for the artificial ammonia synthesis.One critical aspect to unlocking this technology is to discover the catalysts with high selectivity and efficiency.In this work,the N_(2)-to-NH_(3)conversion on the functional MoS_(2)is fully investigated by density functional theory calculations since the layered MoS_(2)provides the ideal platform for the elaborating copies of the nitrogenase found in nature,wherein the functionalization is achieved via basal-adsorption,basal-substitution or edge-substitution of transition metal elements.Our results reveal that the edge-functionalization is a feasible strategy for the activity promotion;however,the basal-adsorption and basal-substitution separately suffer from the electrochemical instability and the NRR inefficiency.Specifically,MoS_(2)functionalized via edge W-substitution exhibits an exceptional activity.The energetically favored reaction pathway is through the distal pathway and a limiting potential is less than 0.20 V.Overall,this work escalates the rational design of the high-effective catalysts for nitrogen fixation and provides the explanation why the predicated catalyst have a good performance,paving the guidance for the experiments.
基金Supported by The Ligue Nationale contre le Cancer,to Puisieux A
文摘Growing evidence suggests that breast cancer cell plasticity arises due to a partial reactivation of epithelialmesenchymal transition(EMT) programs in order to give cells pluripotency, leading to a stemness-like phenotype. A complete EMT would be a dead end program that would render cells unable to fully metastasize to distant organs. Evoking the EMT-mesenchymal-toepithelial transition(MET) cascade promotes successful colonization of distal target tissues. It is unlikely that direct reprogramming or trans-differentiation without passing through a pluripotent stage would be thepreferred mechanism during tumor progression. This review focuses on key EMT transcriptional regulators, EMT-transcription factors involved in EMT(TFs) and the mi RNA pathway, which are deregulated in breast cancer, and discusses their implications in cancer cell plasticity. Cross-regulation between EMT-TFs and mi RNAs, where mi RNAs act as co-repressors or co-activators, appears to be a pivotal mechanism for breast cancer cells to acquire a stem cell-like state, which is implicated both in breast metastases and tumor recurrence. As a master regulator of mi RNA biogenesis, the ribonuclease type Ⅲ endonuclease Dicer plays a central role in EMTTFs/mi RNAs regulating networks. All these EMT-MET key regulators represent valuable new prognostic and predictive markers for breast cancer as well as promising new targets for drug-resistant breast cancers.
基金Supported by INSERM,the SociétéFrancophone du Diabètean Agence Nationale de la Recherche grant project(Crisalis)
文摘In healthy people,balance between glucose production and its utilization is precisely controlled.When circulating glucose reaches a critical threshold level,pancreaticβcells secrete insulin that has two major actions:to lower circulating glucose levels by facilitating its uptake mainly into skeletal muscle while inhibiting its production by the liver.Interestingly,dietary triglycerides are the main source of fatty acids to fulfill energy needs of oxidative tissues.Normally,the unconsumed fraction of excess of fatty acids is stored in lipid droplets that are localized in adipocytes to provide energy during fasting periods.Thus,adipose tissue acts as a trap for fatty acid excess liberated from plasma triglycerides.When the buffering action of adipose tissue to store fatty acids is impaired,fatty acids that build up in othertissues are metabolized as sphingolipid derivatives such as ceramides.Several studies suggest that ceramides are among the most active lipid second messengers to inhibit the insulin signaling pathway and this review describes the major role played by ceramide accumulation in the development of insulin resistance of peripherals tissues through the targeting of specific proteins of the insulin signaling pathway.
基金Supported by Rosell-Lallemand Institute,France and Probi AB,Sweden
文摘AIM:To assess the symptomatic efficacy of Lactobacillus plantarum 299v(L.plantarum 299v)(DSM 9843) for the relief of abdominal symptoms in a large subset of irritable bowel syndrome(IBS) patients fulfilling the Rome Ⅲ criteria.METHODS:In this double blind,placebo-controlled,parallel-designed study,subjects were randomized to daily receive either one capsule of L.plantarum 299v(DSM 9843) or placebo for 4 wk.Frequency and intensity of abdominal pain,bloating and feeling of incomplete rectal emptying were assessed weekly on a visual analogue scale while stool frequency was calculated.RESULTS:Two hundred and fourteen IBS patients were recruited.After 4 wk,both pain severity(0.68 + 0.53 vs 0.92 + 0.57,P < 0.05) and daily frequency(1.01 + 0.77 vs 1.71 + 0.93,P < 0.05) were lower with L.plantarum 299v(DSM 9843) than with placebo.Similar results were obtained for bloating.At week 4,78.1 % of the patients scored the L.plantarum 299v(DSM 9843) symptomatic effect as excellent or good vs only 8.1 % for placebo(P < 0.01).CONCLUSION:A 4-wk treatment with L.plantarum 299v(DSM 9843) provided effective symptom relief,particularly of abdominal pain and bloating,in IBS patients fulfilling the Rome Ⅲ criteria.
基金Supported by"Institut National de la Sante et de la Recherche Médicale"(Inserm)"Centre National de la Recherche Scientifique"(CNRS)"la Ligue Nationale contre le Cancer"(Committees 59,60 and 62)
文摘The recent discovery of cancer cell plasticity,i.e.their ability to reprogram into cancer stem cells(CSCs)either naturally or under chemotherapy and/or radiotherapy,has changed,once again,the way we consider cancer treatment.If cancer stemness is a reversible epigenetic state rather than a genetic identity,opportunities will arise for therapeutic strategies that remodel epigenetic landscapes of CSCs.However,the systematic use of DNA methyltransferase and histone deacetylase inhibitors,alone or in combination,in advanced solid tumors including colorectal cancers,regardless of their molecular subtypes,does not seem to be the best strategy.In this review,we first summarize the knowledge researchers have gathered on the epigenetic signatures of CSCs with the difficulty of isolating rare populations of cells.We raise questions about the relevant use of currently available epigenetic inhibitors(epidrugs)while the expression of numerous cancer stem cell markers are often repressed by epigenetic mechanisms.These markers include the three cluster of differentiation CD133,CD44 and CD166 that have been extensively used for the isolation of colon CSCs.and.Finally,we describe current treatment strategies using epidrugs,and we hypothesize that,using correlation tools comparing associations of relevant CSC markers with chromatin modifier expression,we could identify better candidates for epienzyme targeting.
基金Supported by Agence Nationale de Recherche sur le Sida et les hépatites(ANRS,France),Ligue contre le cancer,France
文摘Hepatitis C virus(HCV) infects hepatocytes, polarized cells in the liver. Chronic HCV infection often leads to steatosis, fibrosis, cirrhosis and hepatocellular carcinoma, and it has been identified as the leading cause of liver transplantation worldwide. The HCV replication cycle is dependent on lipid metabolism and particularly an accumulation of lipid droplets in host cells. Phosphoinositides(PIs) are minor phospholipids enriched in different membranes and their levels are tightly regulated by specific PI kinases and phosphatases. PIs are implicated in a vast array of cellular responses that are central to morphogenesis, such as cytoskeletal changes, cytokinesis and the recruitment of downstream effectors to govern mechanisms involved in polarization and lumen formation. Important reviews of the literature identified phosphatidylinositol(Ptd Ins) 4-kinases, and their lipid products Ptd Ins(4)P, as critical regulators of the HCV life cycle. SH2-containing inositol polyphosphate 5-phosphatase(SHIP2), phosphoinositide 3-kinase(PI3K) and their lipid products Ptd Ins(3,4)P2 and Ptd Ins(3,4,5)P3, respectively, play an important role in the cell membrane and are key to the establishment of apicobasal polarity and lumen formation. In this review, we will focus on these new functions of PI3 K and SHIP2, and their deregulation by HCV, causing a disruption of apicobasal polarity, actin organization and extracellular matrix assembly. Finally we will highlight the involvement of this pathway in the event of insulin resistance and nonalcoholic fatty liver disease related to HCV infection.
基金supported by institutional funding from INSERM(Paris,France)the Aix-Marseille University(Marseille,France)by a grant INCAa-DGSO-INSERM 6038 from sites de recherche intégrésur le cancer(SIRIC)
文摘Few studies have analyzed the effect of ve- nous thromboembolism (VTE) events on the prognosis of pancreatic cancer, but their results were conflicting. The pres- ent study was undertaken to determine the effect of VTE on pancreatic adenocarcinoma (PA) outcomes. METHODS: All consecutive patients diagnosed with PA from May 2004 to January 2012 in a single oncology center were retrospectively studied. Clinical, radiological and histologi- cal data at time of diagnosis or within the first 3 months after surgery, including the presence (+) or absence (-) of VTE were collected. VTE was defined as radiological evidence of either pulmonary embolism (PE), deep venous thrombosis without infection or catheter-related thrombosis. PA with and without PE was compared for survival using the Kaplan-Meier method to estimate overall survival. RESULTS: Among 162 PA patients with a median follow-up of 15 (3-92) months after diagnosis, 28 demonstratedVTE (+). PA patients with and without PE were similar for age, American Society of Anesthesiologist score, body mass index, and histo- ry of treatment. The distribution of cancer stages was similarbetween the two groups VTE (+) and VTE (-). The median du- ration of survival was significantly worse in the VTE (+) group vs VTE (-) (12 vs 18 months, P=0.010). In multivariate analysis, the presence of VTE and surgical treatment were independent prognostic factors for overall survival. CONCLUSION: VTE (+) at time of diagnosis or within the first 3 months after surgery during treatment is an indepen- dent factor of poor prognosis in PA.
文摘Launaea taraxacifolia is a leafy vegetable of the family of Asteraceae (Compositae) found in several countries in West Africa including Ghana, Benin and Nigeria. The plant leaves are eaten either fresh as salad or cooked as sauces. They are also consumed as infusion to fight against several diseases including non-communicable diseases such as diabetes and hypertension. Several studies have been conducted in Ghana, Nigeria on the nutritional and medicinal values of this plant but no study has yet been conducted in Benin on the virtues of this plant. In this work we have achieved the phytochemical characterization and evaluated the cytotoxicity as well as hypolipidemic and anti-oxidant effects of the ethanol-aqueous extracts of Launaea taraxacifolia leaves. Cytotoxicity and hypolipidemic activities have been performed on HepG2 cells;the antioxidant effect has been performed on the PLB985 cells. The results showed that the ethanol-aqueous extracts of Launaea taraxacifolia leaves contained the following metabolites: catechic tannin, flavonoids, phenolic acids, mucilage and leucoanthocyanins. Only very high concentrations (>20 mg/ml) of leaves extracts are toxic for HepG2 cells. Launaea taraxacifolia leaves have significant antioxidant and hypolipidemic activities.
文摘In the world,among all type of cancers,colorectal cancer(CRC)is the third most commonly diagnosed in males and the second in females.In most of cases,(RP1)patients’prognosis limitation with malignant tumors can be attributed to delayed diagnosis of the disease.Identification of patients with early-stage disease leads to more effective therapeutic interventions.Therefore,new screening methods and further innovative treatment approaches are mandatory as they may lead to an increase in progression-free and overall survival rates.For the last decade,the interest in extracellular vesicles(EVs)research has exponentially increased as EVs generation appears to be a universal feature of every cell that is strongly involved in many mechanisms of cell-cell communication either in physiological or pathological situations.EVs can cargo biomolecules,such as lipids,proteins,nucleic acids and generate transmission signal through the intercellular transfer of their content.By this mechanism,tumor cells can recruit and modify the adjacent and systemic microenvironment to support further invasion and dissemination.This review intends to cover the most recent literature on the role of EVs production in colorectal normal and cancer tissues.Specific attention is paid to the use of EVs for early CRC diagnosis,follow-up,and prognosis as EVs have come into the spotlight of research as a high potential source of‘liquid biopsies’.The use of EVs as new targets or nanovectors as drug delivery systems for CRC therapy is also summarized.
文摘There is an increasing interest in developing nanoparticles with diverse biologic activities.To this end,we prepared 10 to 15 nm silver nanoparticles(AgNP)from native isolates of Trichoderma atroviride.Within this study,endophytic fungi hosted four medicinal plants in Saint Katherine Protectorate,South Sinai,Egypt have been isolated by surface sterilization technique on four isolation media.Ten species,based on their frequency of occurrence,out of twenty recovered taxa were tested for their capability to synthesize extracellular AgNPs.Trichoderma atroviride hosted Chiliadenus montanus was found to be the best candidate for the production of mycogenic AgNPs among all examined species.The mycosynthesized AgNPs were compared with chemically synthesized and characterized using Ultraviolet-visible(UV-vis)spectroscopy,Raman spectroscopy,X-ray diffraction(XRD)and high-resolution transmission electron microscopy(HRTEM)techniques.The HRTEM result showed the distribution of spherical AgNPs ranging from 10 to 15 nm.Trichoderma atroviride isolate was subjected to sequencing for confirmation of phenotypic identification.The internal transcribed spacer(ITS)1-5.8 s-ITS2 rDNA sequences obtained were compared with those deposited in the GenBank Database and registered with accession number MH283876 in the NCBI Database.Antibacterial,anticandidal and antifungal effects of chemically and mycosynthesized AgNPs were examined at various concentrations in vitro against six pathogenic bacteria and 4 pathogenic fungi by agar well diffusion technique.Standard antibiotics;Gentamicin,Amoxicillin,Clotrimazole,and Nystatin at 5μg/disk were taken as positive controls,while 5%DMSO was used as the negative control.Our data revealed that the application of mycogenic AgNPs at a concentration of 100 ppm resulted in maximum inhibition of pathogenic bacteria and fungi.These data suggest that AgNPs from native isolates of Trichoderma atroviride(MH283876)offer a source of rapid synthesis of eco-friendly,economical biomaterials that show antimicrobial activities.
基金supported by HECAM (BPI), EBCI, INCa (Wnt HCC project). J-C.N.supported by a fellowship from INCa
文摘Hepatocellular carcinoma(HCC)is one of the leading causes of cancer related death in Asia and Africa(1).It reflects the high burden of hepatitis B virus(HBV)infection in these areas.Curative treatments of HCC as radiofrequency ablation and resection are impaired by a high rate of tumor recurrence.However,most of the time,HCC is frequently diagnosed at advanced stages where only
文摘The Beni Bousera massif(Rifean belt,northern Morocco)is predominantly composed of spinel lherzolite with subordinate garnet pyroxenite and garnet peridotite layers.It formed an antiformal dome which was overlain by graphite-sillimanite-garnet gneisses(kinzigites)equilibrated at around 1 GPa and 750℃.Within these kinzigites,kyanite-bearing basic granulites record somewhat higher PT conditions of around 1.6-2.0 GPa and 760-820℃.Garnet clinopyroxenite(either graphite-bearing or graphi-
文摘AIM:To assess,in a routine practice setting,the sus-tained virologic response(SVR) to telaprevir(TPV) or boceprevir(BOC) in hepatitis C virus(HCV) nullresponders or relapsers with severe liver fibrosis.METHODS:One hundred twenty-five patients were treated prospectively for 48 wk with TPV or BOC + pegylated-interferon(peg-INF) α2a + ribavirin(PR) according to standard treatment schedules without randomization.These patients were treated in routine practice settings in 10 public or private health care centers,and the data were prospectively collected.Only patients with severe liver fibrosis(Metavir scores of F3 or F4 upon liver biopsy or liver stiffness assessed by elastography),genotype 1 HCV and who were null-responders or relapsers to prior PR combination therapy were included in this study.RESULTS:The Metavir fibrosis scores were F3 in 35(28%) and F4 in 90(72%) of the patients.In total,62.9% of the patients were null-responders and 37.1% relapsers to the previous PR therapy.The overall SVR rate at 24 wk post-treatment withdrawal was 59.8%.The SVR was 65.9% in the TPV group and 44.1% in the BOC group.Independent predictive factors of an SVR included a response to previous treatment,relapsers vs null-responders [OR = 3.9;(1.4,10.6),P = 0.0084],a rapid virological response(RVR) [OR 6.9(2.6,18.2),P = 0.001] and liver stiffness lower than 21.3 kPa [OR = 8.2(2.3,29.5),P = 0.001].During treatment,63 patients(50.8%) had at least one severe adverse event(SAE) of grade 3 or 4.A multivariate analysis identified two factors associated with SAEs:female gender [OR = 2.4(1.1,5.6),P = 0.037] and a platelet count below 150 × 103/ mm3 [OR = 5.3(2.3,12.4),P ≤ 0.001].CONCLUSION:More than half of these difficult-to-treat patients achieved an SVR and had SAEs in an actual practice setting.The SVR rate was influenced by the response to previous PR treatment,the RVR and liver stiffness.
文摘In this work, we study the smoothing effect of Cauchy problem in Sobolev space for the spatially homogeneous Landau equation in the Maxwellian case. We obtain a precise estimate with respect to time variable, which implies the ultra-analytic effect of weak solutions.
基金the financial support from Electricitéde France(EDF)within the framework of the Generation II&III nuclear reactor research program。
文摘The presence of solid particles or water droplets in continuous fluid flow can either induce turbulence attenuation or amplification. The modification of the state of the turbulence depends on the characteristics of the particles, such as volume fraction, mean diameter, mass density, or carrier phase flow properties. In this brief review, the main physical concepts related to the most important physical aspects of turbulence modulation are summarized. Different criteria used to distinguish the enhancement or the attenuation effects of the particles on the carrier phase flows are recalled. For the interest of large-scale industrial applications, several theoretical,experimental and empirical approaches are discussed, which provides an interesting framework for the study of the effect of particles on turbulence behavior modification.
文摘This review is concerned with the effect of the addition of zirconium as a third element on the heat-resisting properties of Fe_3Al intermetallic compounds and explains their high-temperature oxidation mechanism.The Fe_3Al and Fe_3Al-0.05Zr specimens were isothermally oxidized in the temperature range of 1173~1473 K in synthetic air for 100 h.The formation of the alumina layer approximately obeyed the parabolic rate law,with the exception of short initial stage.The parabolic rate constant values for the Zr-doped Fe_3Al decreased at all tested temperatures.Fe_3Al revealed massive spallation,whereas Fe_3AlZr produced a flat,adherent oxide layer.The microstructure investigations of the alumina scales grown thermally on the Fe_3Al-Zr alloy by means of SEM-EDS showed that they were 1.5~2μm thick and consisted of a small inner columnar layer and an equiaxed outer grain layer.Additionally,very fine(50~150 nm) oxide particles rich in Zr were found across the alumina scales.The addition of Zr significantly affected the oxidation behavior of Fe_3Al by improving the adherence of theα-Al_2O_3 scale.TEM-SAD investigations of the alumina scales on samples prepared using the FIB(Focused Ion Beam) method confirmed the presence of small tetragonal zirconia grains near the scale/gas and alloy/scale interfaces,most of which were formed along alumina grain boundaries(gbs).Zr gb-segregation was found using HRTEM.The role of preferential formation of zirconium oxide along the alumina scale grain boundaries and the effect of Zr gb-segregation on oxidation and scale growth mechanisms were analyzed by means of two-stage oxidation experiments using ^(16)O_2/^(18)O_2.The SIMS oxygen isotope profiles for the Fe_3Al-Zr alloy oxidized at 1373 K, after two-stage oxidation experiments,revealed that oxygen anion diffusion is predominant compared to that of aluminum cation diffusion.
文摘BACKGROUND When combined with vanadium salts,catecholamines strongly activate glucose uptake in rat and mouse adipocytes.AIM To test whether catecholamines activate glucose transport in human adipocytes.METHODS The uptake of 2-deoxyglucose(2-DG)was measured in adipocytes isolated from pieces of abdominal subcutaneous tissue removed from women undergoing reconstructive surgery.Pharmacological approaches with amine oxidase inhibitors,adrenoreceptor agonists and antioxidants were performed to unravel the mechanisms of action of noradrenaline or adrenaline(also named epinephrine).RESULTS In human adipocytes,45-min incubation with 100μmol/L adrenaline or noradrenaline activated 2-DG uptake up to more than one-third of the maximal response to insulin.This stimulation was not reproduced with millimolar doses of dopamine or serotonin and was not enhanced by addition of vanadate to the incubation medium.Among various natural amines and adrenergic agonists tested,no other molecule was more efficient than adrenaline and noradrenaline in stimulating 2-DG uptake.The effect of the catecholamines was not impaired by pargyline and semicarbazide,contrarily to that of benzylamine or methylamine,which are recognized substrates of semicarbazide-sensitive amine oxidase.Hydrogen peroxide at 1 mmol/L activated hexose uptake but not pyrocatechol or benzoquinone,and only the former was potentiated by vanadate.Catalase and the phosphoinositide 3-kinase inhibitor wortmannin inhibited adrenaline-induced activation of 2-DG uptake.CONCLUSION High doses of catecholamines exert insulin-like actions on glucose transport in human adipocytes.At submillimolar doses,vanadium did not enhance this catecholamine activation of glucose transport.Consequently,this dismantles our previous suggestion to combine the metal ion with catecholamines to improve the benefit/risk ratio of vanadium-based antidiabetic approaches.
文摘Along with the development of big data, various Natural Language Generation systems (NLGs) have recently been developed by different companies. The aim of this paper is to propose a better understanding of how these systems are designed and used. We propose to study in details one of them which is the NLGs developed by the company Nomao. First, we show the development of this NLGs underlies strong economic stakes since the business model of Nomao partly depends on it. Then, thanks to an eye movement analysis conducted with 28 participants, we show that the texts generated by Nomao’s NLGs contain syntactic and semantic structures that are easy to read but lack socio-semantic coherence which would improve their understanding. From a scientific perspective, our research results highlight the importance of socio-semantic coherence in text-based communication produced by NLGs.